Regulation of B-cell function and expression of CD11c, T-bet, and FcRL5 in response to different activation signals

Eur J Immunol. 2024 Aug;54(8):e2350736. doi: 10.1002/eji.202350736. Epub 2024 May 3.

Abstract

CD11c, FcRL5, or T-bet are commonly expressed by B cells expanding during inflammation, where they can make up >30% of mature B cells. However, the association between the proteins and differentiation and function in the host response remains largely unclear. We have assessed the co-expression of CD11c, T-bet, and FcRL5 in an in vitro B-cell culture system to determine how stimulation via the BCR, toll-like receptor 9 (TLR9), and different cytokines influence CD11c, T-bet, and FcRL5 expression. We observed different expression dynamics for all markers, but a largely overlapping regulation of CD11c and FcRL5 in response to BCR and TLR9 activation, while T-bet was strongly dependent on IFN-γ signaling. Investigating plasma cell differentiation and APC functions, there was no association between marker expression and antibody secretion or T-cell help. Rather the functions were associated with TLR9-signalling and B-cell-derived IL-6 production, respectively. These results suggest that the expression of CD11c, FcRL5, and T-bet and plasma cell differentiation and improved APC functions occur in parallel and are regulated by similar activation signals, but they are not interdependent.

Keywords: Atypical B cells; B cells; CD11c; Double‐negative B cells; FcRL5; Malaria; T‐bet.

MeSH terms

  • Animals
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / metabolism
  • CD11c Antigen* / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Gene Expression Regulation / immunology
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-6 / metabolism
  • Lymphocyte Activation* / immunology
  • Mice
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Fc / immunology
  • Receptors, Fc / metabolism
  • Signal Transduction / immunology
  • T-Box Domain Proteins* / genetics
  • T-Box Domain Proteins* / metabolism
  • Toll-Like Receptor 9* / immunology
  • Toll-Like Receptor 9* / metabolism

Substances

  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • CD11c Antigen
  • Toll-Like Receptor 9
  • Receptors, Fc
  • Interferon-gamma
  • Receptors, Antigen, B-Cell
  • FCRL5 protein, human
  • Interleukin-6